An unusual case of aggregatibacter aphrophilus liver abscess

An unusual case of aggregatibacter aphrophilus liver abscess

Ilias Papakonstantinou^1,&, Zoi Psaroudaki², Efstathia Perivolioti²

 

¹4^th Department of Internal Medicine, "Evangelismos" General Hospital of Athens, Athens, Greece, ²Department of Clinical Microbiology, "Evangelismos" General Hospital of Athens, Athens, Greece

 

 

^&Corresponding author
Ilias Papakonstantinou, 4^th Department of Internal Medicine, "Evangelismos" General Hospital of Athens, Athens, Greece

 

 

 

 

Aggregatibacter aphrophilus (A. aphrophilus), belonging to the aggregatibacter genus, is a gram-negative aerobic rod of the normal mixed oropharyngeal flora in humans, and most frequently represent a colonizer of oral mucocutaneous surfaces, like the supragingival plaque with no or limited pathogenicity [1,2]. Life-threatening invasive disease is rare. Aggregatibacter spp can be a prominent etiology of infective endocarditis and specifically A. aphrophilus exhibit an important cause of brain abscesses [1,3]. In this manuscript, we present a case of a previously healthy and immunocompetent person with A. aphrophilus liver abscess without predisposing conditions, which is an otherwise uncommon causative agent in healthy individuals.

 

 

A 23-year-old previously healthy man, presented to the hospital's emergency department, with a 3-day history of high-grade fever up to 40°C and upper right abdominal pain. The patient's past medical history was non-significant. He was a student and had not received any medication. He had a pet dog and reported no recent travel. During physical examination on admission, vital signs were normal and he was febrile with a body temperature of 38°C. Abdominal examination revealed a tender palpable liver, with no signs of peritoneal irritation. The remainder of physical examination was unremarkable. Abnormal laboratory results on admission included a white blood cell count (WBC) of 20.830 (4-10.5x10³/μL), elevated C-reactive protein (CRP) level (28mg/dl, normal ≤0.5mg/dl), slightly elevated alanine aminotransferase (ALT) of 56 IU/L (normal 5-40 IU/L), and lactic dehydrogenase (LDH) of 255 IU/L (normal <225 IU/L). Alkaline phosphatase (ALP) was normal. Abdominal ultrasonography on admission revealed a mildly enlarged liver and spleen and the presence of 2 sizable, hypoechoic lesions. Abdominal computed tomography (CT) scan revealed the 2 aforementioned lesions in diameter of 5.6cm at the left liver lobe and 5.2cm in the right lobe Figure 1, Figure 2.

 

The lesions were hypodense and presented peripheral enhancement after intravenous contrast, similar to the morphology of hepatic abscesses. The patient was admitted for further evaluation and treatment. Culture guided antimicrobials and appropriate drainage was our first option. Empiric antibiotic therapy with intravenous ciprofloxacin (400mg every 12 hours), and metronidazole (500mg every 8 hours) was initiated. All cultures resulted negative. Initially, we performed percutaneous sonographic (U/S) guided aspiration into the left hepatic abscess cavity. A thick, purulent material of 40cc was drained and sent for culture. Microbiology revealed a Gram-negative bacterium that presented slow growth. On the 5^th and 8^th days of admission, we performed CT guided catheter drainage of both abscesses. Meanwhile irregular spikes of fever with daytime variation accompanied by night sweats persisted. Ciprofloxacin discontinued and meropenem at a dose of 1gr every 8 hours administered. Thorough screening for other possible sources of infection, resulted negative. Transthoracic echocardiography was negative for vegetations and showed mild mitral regurgitation. Entamoeba histolytica Abs, echinococcus Abs, leismania Abs, brucella Abs were negative. Gastrointestinal endoscopic evaluation was unrevealing. The patient was also HIV negative and no other immunodeficiency conditions were identified. Eventually, the isolate identified by the Vitek 2 automated system and classified as A. aphrophilus. To confirm the identification of the strain we performed matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The sensitivity test was performed with minimal inhibitory concentration (MIC) test strips; the isolate's susceptibility was to ceftriaxone ≤0.125 (S), cefepime ≤0.5 (S), ciprofloxacin ≤0.125 (S), gentamycin ≤0.5 (S), amikacin ≤0.125 (S) and to meropenem ≤0.032 (S). Percutaneous drainage of both abscesses, combined with antimicrobial treatment, was successful and the patient's clinical condition improved. Thankfully, no surgical procedure was required. The drains were removed immediately the fluid from the abscess cavities became clear. Meropenem was administered for a total of 2 weeks. Then meropenem was switched to oral ciprofloxacin for another 4 weeks and the patient was discharged from the hospital, in full recovery. Follow-up sonogram obtained almost 2 months after the drainage showed completely normal liver parenchyma without any residual liver cavities.

 

 

This is only one of the few reported cases of hepatic abscess formation by A. aphrophilus and one of the first in a healthy individual without significant oral pathology. An overview of 3 relevant cases with aggregatibacter spp related liver abscesses was found in the literature, and is presented on Table 1 [4-6]. A. aphrophilus, as the cause of liver abscesses in our patient, originated from the oropharyngeal region. The oral microbiome is abundant and composed with a diverse collection of organisms [7]. Among the major phyla that dominate bacterial oral community, the most important and predominant oral genera that are associated with liver abscesses include: actinomyces, rothia (actinobacteria), prevotella, bacteroides, porphyromonas, capnocytophaga (bacteroidetes), fusobacterium (fusobacteria), veillonella (firmicutes) and the streptococcus millieri group [7,8]. The metastatic mode of transmission to the liver, through hematogenous seeding of a distally located infectious source is relatively uncommon, especially if originating from the oral cavity [8]. A. aphrophilus initially localized the oropharynx and then under certain conditions, a covert bacteremia occured, leading to septic spread and metastatic abscess formation to the liver. Several mechanisms may contributed to evade this organism patient's host defense and cause an invasive infection e.g transient immunodeficiency from viral illness, possible alcohol consumption. A potentially zoonotic transmission of A. aphrophilus from his dog cannot be supported, since interactions of canine oral bacteria and the human's oral environment are difficult and the distribution of periodontopathic species in both humans and animals is generally different [9,10]. Distant infection and abscess formation is very likely to be associated with specific A. aphrophilus virulence properties, enabling immunological escape mechanisms. Ohyama et al have found through immunohistochemical staining, that periodontopathic bacteria can be carried in different organs [8]. From recent genome sequence research, Nørskov-Lauritsen remarks that A. aphrophilus express long filamentous fibrils and adhesins, that may participate in host colonization and potential opportunistic invasion of epithelial cells, proteolytic enzymes and toxins production are not mentioned though [1,2].

 

 

In this report, we presented a case of multiple liver abscesses without any apparent contiguous or distal source of infection, attributed to an uncommon pathogen of oropharyngeal origin, the A. aphrophilus. The microbiologic diagnosis of A. aphrophilus was challenging due to slow growth under laboratory conditions. Treatment achived by combined use of antimicrobials with liver abscess percutaneous catheter drainage. This is one of the first reported cases of A. aphrophilus multiple liver abscesses in healthy persons, without underlying predisposing factors, suggesting that rare and under-recognized etiologic agents of liver abscess do occur. Physicians awareness and laboratory vigilance are required for appropriate detection and favorable outcome.

 

 

The authors declare no competing interests.

 

 

All authors read and approved the final version of this manuscript.

 

 

Table 1: reported cases of hepatic abscesses caused by aggregatibacter species

Figure 1: abdominal computed tomography (CT) showing an abscess in the left hepatic lobe

Figure 2: abdominal computed tomography (CT) showing an abscess in the right hepatic lobe

 

 

1. Nørskov-Lauritsen N. Classification, identification, and clinical significance of haemophilus and aggregatibacter species with host specificity for humans. Clin Microbiol Rev. 2014;27(2):214-240. PubMed | Google Scholar


2. Di Bonaventura MP, DeSalle R, Pop M, Nagarajan N, Figurski DH, Fine DH et al. Complete genome sequence of aggregatibacter (Haemophilus) aphrophilus NJ8700. J Bacteriol. 2009;191(14):4693-4694. PubMed | Google Scholar


3. Chambers ST, Murdoch D, Morris A, Holland D, Pappas P, Almela M et al. HACEK infective endocarditis: characteristics and outcomes from a large, multi-national cohort. PLoS One. 2013;8(5):e63181. PubMed | Google Scholar


4. Tsui K, Tsai CR, Lin LC, Yang CC, Huang CH. Aggregatibacter aphrophilus pyogenic liver abscess in an immunocompetent young woman. J Microbiol Immunol Infect. 2012;45(5):385-389. PubMed | Google Scholar


5. Sherlock M, Roche M, Agha A, Smyth E, Thompson CJ. A case of haemophilus aphrophilus and mobiluncus mulieris hepatic abscess. J Infect. 2005;51(2):E19-22. PubMed | Google Scholar


6. Ariyaratnam S, Gajendragadkar PR, Dickinson RJ, Roberts P, Harris K, Carmichael A et al. Liver and brain abscess caused by aggregatibacter paraphrophilus in association with a large patent foramen ovale: a case report. J Med Case Rep. 2010;4:69. PubMed | Google Scholar


7. Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH et al. The human oral microbiome. J Bacteriol. 2010;192(19):5002-5017. PubMed | Google Scholar


8. Ohyama H, Nakasho K, Yamanegi K, Noiri Y, Kuhara A, Kato-Kogoe N et al. An unusual autopsy case of pyogenic liver abscess caused by periodontal bacteria. Jpn J Infect Dis. 2009;62(5):381-383. PubMed | Google Scholar


9. Yamasaki Y, Nomura R, Nakano K, Naka S, Matsumoto-Nakano M, Asai F et al. Distribution of periodontopathic bacterial species in dogs and their owners. Arch Oral Biol. 2012;57(9):1183-1188. PubMed | Google Scholar


10. Oh C, Lee K, Cheong Y, Lee SW, Park SY, Song CS et al. Comparison of the oral microbiomes of canines and their owners using next-generation sequencing. PLoS One. 2015;10(7):e0131468. PubMed | Google Scholar